Infection with a bacterium, Helicobacter pylori, has been identified as a risk factor for gastric cancer. Dietary ascorbic acid appears to protect against this malignancy. Recently, H. pylori infection has been shown to dramatically diminish ascorbic acid levels within the stomach even when plasma levels are normal. We hypothesize that the damaging effects of H. pylori are mediated by increased cell proliferation, increased production of inflammation-related free radicals, and increased N-nitrosation of nitrites. We further hypothesize that these latter two effects are in part attributable to H. pylori-related decreases in intragastric ascorbic acid concentration and that eradication of H. pylori infection can reduce cancer risk. An efficient way to assess the impact of H. pylori on gastric cancer risk is to evaluate the effect of H. pylori eradication on intermediate, preneoplastic lesions. If elimination of infection causes preneoplastic mucosa to return to normal then it seems probable that gastric cancer risk would also diminish. Two preneoplastic lesions appear to be addressable: atrophic gastritis and intestinal metaplasia. In the future, we hope to evaluate the effects of anti-H. pylori therapy and ascorbic acid on intermediate lesions in a large, randomized, double- blind placebo control trial. In preparation for this study, we propose to validate and refine the endoscopic and laboratory techniques necessary for monitoring intestinal metaplasia and ascorbic acid concentrations.